LOX-l but not RAGE mRNA and protein levels were up-regulated in rats exposed to ozone, whereas RAGE and HMGB-1 mRNA increased only in rats exposed to ozone + DEP.
HMGB-1, recently known as the "late" proinflammatory mediator of systemic inflammation, has been shown to activate MAP kinase and NF[kappa]B signaling through RAGE (Sims et al.
The Company's current research and development portfolio includes the following therapeutic targets: HMGB-1
, a pro-inflammatory substance identified as a mediator of TNF-associated tissue damage; development of small molecule and vagal nerve stimulation approaches to treat inflammation; and CTI-01, a proprietary anti-inflammatory drug candidate currently in Phase I clinical trials.
The companies plan to focus on developing drug products with the potential to block HMGB-1, which if successful, could help reduce the injury and death associated with severe inflammatory diseases and infections.
Elevated levels of HMGB-1 are found in many acute and chronic diseases, including rheumatoid arthritis, inflammatory bowel disease, hemorrhagic shock, sepsis, endotoxemia, and acute lung injuries.
HMGB-1 is a cytokine, which means it is one of the many hormone-like proteins secreted by different cell types that regulate the intensity and duration of an immune response.